Helminthic therapy

Helminthic therapy

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Helminthic therapy, a type of immunotherapy
Immunotherapy
Immunotherapy is a medical term defined as the "treatment of disease by inducing, enhancing, or suppressing an immune response". Immunotherapies designed to elicit or amplify an immune response are classified as activation immunotherapies. While immunotherapies that reduce or suppress are...

, is the treatment of autoimmune disease
Autoimmune disease
Autoimmune diseases arise from an overactive immune response of the body against substances and tissues normally present in the body. In other words, the body actually attacks its own cells. The immune system mistakes some part of the body as a pathogen and attacks it. This may be restricted to...

s and immune disorder
Immune disorder
An immune disorder is a dysfunction of the immune system. These disorders can be characterized in several different ways:* By the component of the immune system affected* By whether the immune system is overactive or underactive...

s by means of deliberate infestation with a helminth or with the ova of a helminth. Helminths are parasitic worm
Parasitic worm
Parasitic worms or helminths are a division of eukaryoticparasites that, unlike external parasites such as lice and fleas, live inside their host. They are worm-like organisms that live and feed off living hosts, receiving nourishment and protection while disrupting their hosts' nutrient...

s such as hookworms and whipworms.

Helminthic therapy consists of the inoculation
Inoculation
Inoculation is the placement of something that will grow or reproduce, and is most commonly used in respect of the introduction of a serum, vaccine, or antigenic substance into the body of a human or animal, especially to produce or boost immunity to a specific disease...

 of the patient with specific parasitic intestinal nematodes (helminths). There are currently three closely related treatments available. Inoculation with Necator americanus
Necator americanus
Necator americanus is a species of Necator. It is a class within the phylum Nematodes and commonly known as New World hookworm. It is a parasitic nematode worm that lives in the small intestine of hosts such as humans, dogs and cats. It is responsible for Necatoriasis...

, commonly known as hookworm
Hookworm
The hookworm is a parasitic nematode that lives in the small intestine of its host, which may be a mammal such as a dog, cat, or human. Two species of hookworms commonly infect humans, Ancylostoma duodenale and Necator americanus. A. duodenale predominates in the Middle East, North Africa, India...

s, or Trichuris suis
Trichuris suis
Trichuris suis is a whipworm; the variations in thickness of the anterior and posterior segments give the parasite the characteristic “whip-like” appearance. Adult females measure 6 to 8 cm and adult males 3 to 4 cm. T. suis eggs are oval and yellow-brown with bipolar plugs.T...

ova (TSO), commonly known as pig whipworm
Whipworm
The human tapworm is a roundworm, which causes trichuriasis when it infects a human large intestine. The name whipworm refers to the shape of the worm; they look like whips with wider "handles" at the posterior end.-Life cycle:The female T. trichiura produces 2,000–10,000 single celled eggs per day...

 eggs, or inoculation with Trichuris trichiura ova, commonly referred to as human whipworm eggs.

Current research and available therapy are targeted at, or available for, the treatment of Crohn’s disease, ulcerative colitis
Ulcerative colitis
Ulcerative colitis is a form of inflammatory bowel disease . Ulcerative colitis is a form of colitis, a disease of the colon , that includes characteristic ulcers, or open sores. The main symptom of active disease is usually constant diarrhea mixed with blood, of gradual onset...

, inflammatory bowel disease
Inflammatory bowel disease
In medicine, inflammatory bowel disease is a group of inflammatory conditions of the colon and small intestine. The major types of IBD are Crohn's disease and ulcerative colitis.-Classification:...

 (IBD), multiple sclerosis
Multiple sclerosis
Multiple sclerosis is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms...

, asthma
Asthma
Asthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath...

, eczema
Eczema
Eczema is a form of dermatitis, or inflammation of the epidermis . In England, an estimated 5.7 million or about one in every nine people have been diagnosed with the disease by a clinician at some point in their lives.The term eczema is broadly applied to a range of persistent skin conditions...

, dermatitis
Dermatitis
-Etymology:Dermatitis derives from Greek derma "skin" + -itis "inflammation" and genetic disorder.-Terminology:There are several different types of dermatitis. The different kinds usually have in common an allergic reaction to specific allergens. The term may describe eczema, which is also called...

, hay fever
Hay Fever
Hay Fever is a comic play written by Noël Coward in 1924 and first produced in 1925 with Marie Tempest as the first Judith Bliss. Laura Hope Crews played the role in New York...

 and food allergies
Food allergy
A food allergy is an adverse immune response to a food protein. They are distinct from other adverse responses to food, such as food intolerance, pharmacological reactions, and toxin-mediated reactions....

.

Helminthic infection has emerged as one possible explanation for the low incidence of autoimmune diseases and allergies in less developed countries, together with the significant and sustained increase in autoimmune diseases in industrialized countries.

Incidence of autoimmune diseases and parasitic infestation


While it is recognized that there is probably a genetic disposition in certain individuals for the development of autoimmune diseases, the rate of increase in incidence
Incidence (epidemiology)
Incidence is a measure of the risk of developing some new condition within a specified period of time. Although sometimes loosely expressed simply as the number of new cases during some time period, it is better expressed as a proportion or a rate with a denominator.Incidence proportion is the...

 of autoimmune diseases cannot be explained by genetics alone. There is evidence that one of the primary reasons for the increase in autoimmune diseases in the industrialized nations is the significant change in environmental factors over the last century. Environmental factors include exposure to certain artificial chemicals from industrial processes, medicines, farming and food preparation. It is posited that the absence of exposure to certain parasites, bacteria and viruses is playing a significant role in the development of autoimmune diseases in the more sanitized Western industrialized nations.

Lack of exposure to naturally occurring pathogens and parasites may result in an increased incidence of autoimmune diseases. This is consistent with the hygiene hypothesis
Hygiene hypothesis
In medicine, the Hygiene Hypothesis states that a lack of early childhood exposure to infectious agents, symbiotic microorganisms , and parasites increases susceptibility to allergic diseases by suppressing natural development of the immune system...

. A complete explanation of how environmental factors play a role in autoimmune diseases has still not been proposed. However epidemiological studies, such as the meta analysis by Leonardi-Bee et al., have helped to establish the link between parasitic infestation and its protective role in autoimmune disease development.

Some recent research appears to confirm that the central tenet of the hygiene hypothesis
Hygiene hypothesis
In medicine, the Hygiene Hypothesis states that a lack of early childhood exposure to infectious agents, symbiotic microorganisms , and parasites increases susceptibility to allergic diseases by suppressing natural development of the immune system...

 is true — that parasites, and in particular helminths, have shaped the evolution of at least parts of the human immune system, and even the genes responsible for Crohn's disease
Crohn's disease
Crohn's disease, also known as regional enteritis, is a type of inflammatory bowel disease that may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms...

, ulcerative colitis
Ulcerative colitis
Ulcerative colitis is a form of inflammatory bowel disease . Ulcerative colitis is a form of colitis, a disease of the colon , that includes characteristic ulcers, or open sores. The main symptom of active disease is usually constant diarrhea mixed with blood, of gradual onset...

 and celiac disease — and provides further evidence that it is the absence of parasites, and in particular helminths, that has caused a substantial portion of the increase in incidence of diseases of immune dysregulation and inflammation in industrialized countries in the last century.

Theoretical explanation


Although the mechanism of autoimmune disease
Autoimmune disease
Autoimmune diseases arise from an overactive immune response of the body against substances and tissues normally present in the body. In other words, the body actually attacks its own cells. The immune system mistakes some part of the body as a pathogen and attacks it. This may be restricted to...

 development is not fully defined, there is broad agreement that the majority of autoimmune diseases are caused by inappropriate immunological responses to innocuous antigens, driven by a branch of the immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...

 known as the TH1 type immune response
T helper cell
T helper cells are a sub-group of lymphocytes, a type of white blood cell, that play an important role in the immune system, particularly in the adaptive immune system. These cells have no cytotoxic or phagocytic activity; they cannot kill infected host cells or pathogens. Rather, they help other...

. Extra-cellular antigens primarily trigger the TH2 response, as observed with allergies, while intracellular antigens trigger a TH1 response. The relationship between these two types of immune response is a central theme of the hygiene hypothesis
Hygiene hypothesis
In medicine, the Hygiene Hypothesis states that a lack of early childhood exposure to infectious agents, symbiotic microorganisms , and parasites increases susceptibility to allergic diseases by suppressing natural development of the immune system...

, which suggests that there is a regulatory action between the two types of response. However, the observation that allergies and autoimmune response are increasing at a similar rate in the industrialized nations appears to undermine the hygiene hypothesis.

A refinement of the hygiene hypothesis, which overcomes this apparent contradiction, is the "old friends hypothesis." The old friends hypothesis modifies the hygiene hypothesis by proposing that T regulator cell
Regulatory T cell
Regulatory T cells , sometimes known as suppressor T cells, are a specialized subpopulation of T cells which suppresses activation of the immune system and thereby maintains tolerance to self-antigens. The existence of regulatory T cells was the subject of significant controversy among...

s can only become fully effective if they are stimulated by exposure to microorganisms and parasites that have low levels of pathogenicity, and which have coexisted universally with human beings throughout our evolutionary history. This theory has recently been given more credibility by a study demonstrating the impact of infectious organisms, and helminths in particular, upon genes responsible for the production of various cytokine
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...

s, some involved in the regulation of inflammation, in particular those associated with the development of Crohn's Disease
Crohn's disease
Crohn's disease, also known as regional enteritis, is a type of inflammatory bowel disease that may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms...

, ulcerative colitis
Ulcerative colitis
Ulcerative colitis is a form of inflammatory bowel disease . Ulcerative colitis is a form of colitis, a disease of the colon , that includes characteristic ulcers, or open sores. The main symptom of active disease is usually constant diarrhea mixed with blood, of gradual onset...

, and celiac disease.

The hygiene hypothesis proposes that appropriate immune response is in part learned by exposure to these microorganisms and parasites, and in part regulated by their presence. In the industrialised nations, humans are exposed to somewhat lower levels of these organisms. The development of vaccines, hygienic practices, and effective medical care have diminished or eliminated the prevalence and impact of many parasitic organisms, as well as bacterial and viral infections. This has been of obvious benefit with the effective eradication of many diseases that have plagued human beings. However, while many severe diseases have been eradicated, humans' exposure to benign and apparently beneficial parasites has also been reduced commensurately. The central thrust of the theory is, therefore, that correct development of T regulator cell
Regulatory T cell
Regulatory T cells , sometimes known as suppressor T cells, are a specialized subpopulation of T cells which suppresses activation of the immune system and thereby maintains tolerance to self-antigens. The existence of regulatory T cells was the subject of significant controversy among...

s in individuals may depend on exposure to organisms such as lactobacilli, various mycobacteria, and helminths. Lack of exposure to sufficient benign antigens, particularly during childhood, is sometimes suggested as a cause of the increase in autoimmune diseases and diseases for which chronic inflammation is a major component in the industrialized world.

Research


Helminthic therapy with both hookworm and TSO has been investigated in research published by the University of Nottingham
University of Nottingham
The University of Nottingham is a public research university based in Nottingham, United Kingdom, with further campuses in Ningbo, China and Kuala Lumpur, Malaysia...

 and University of Iowa
University of Iowa
The University of Iowa is a public state-supported research university located in Iowa City, Iowa, United States. It is the oldest public university in the state. The university is organized into eleven colleges granting undergraduate, graduate, and professional degrees...

.

Helminthic therapy is currently being studied as a treatment for several (non-viral) auto-immune diseases including celiac disease, Crohn's disease
Crohn's disease
Crohn's disease, also known as regional enteritis, is a type of inflammatory bowel disease that may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms...

, multiple sclerosis
Multiple sclerosis
Multiple sclerosis is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms...

, and ulcerative colitis
Ulcerative colitis
Ulcerative colitis is a form of inflammatory bowel disease . Ulcerative colitis is a form of colitis, a disease of the colon , that includes characteristic ulcers, or open sores. The main symptom of active disease is usually constant diarrhea mixed with blood, of gradual onset...

.

Hookworms have been found to reduce the risk of developing asthma, while Ascaris lumbricoides
Ascaris lumbricoides
Ascaris lumbricoides is the giant roundworm of humans, belonging to the phylum Nematoda. An ascarid nematode, it is responsible for the disease ascariasis in humans, and it is the largest and most common parasitic worm in humans. One-sixth of the human population is estimated to be infected by this...

(roundworm infection) was associated with an increased risk of asthma.

The authors of a study published in Science Magazine in April of 2011 suggest that there may be a link between the rising rates of metabolic syndrome in the developed worlds and the largely successful efforts of Westerners to eliminate intestinal parasites. The authors' work suggest that eosinophils (a type of white blood cell) in fat tissue play an important role in preventing insulin resistance by secreting interleukin 4, which in turn switches macrophages into "alternative activation." Alternatively activated macrophages are important to maintaining glucose homeostasis (i.e., blood sugar regulation). Helminth infection causes an increase in eosinophils. In the study, the authors fed rodents a high-fat diet in order to induce metabolic syndrome, and then injected them with helminths. Helminth infestation improved the rodents' metabolism. The authors concluded:
"Although sparse in blood of persons in developed countries, eosinophils are often elevated in individuals in rural developing countries where intestinal parasitism is prevalent and metabolic syndrome rare. We speculate that eosinophils may have evolved to optimize metabolic homeostasis during chronic infections by ubiquitous intestinal parasites..."

See also

  • Gut flora
    Gut flora
    Gut flora consists of microorganisms that live in the digestive tracts of animals and is the largest reservoir of human flora. In this context, gut is synonymous with intestinal, and flora with microbiota and microflora....

  • Helminths
  • Hookworm
    Hookworm
    The hookworm is a parasitic nematode that lives in the small intestine of its host, which may be a mammal such as a dog, cat, or human. Two species of hookworms commonly infect humans, Ancylostoma duodenale and Necator americanus. A. duodenale predominates in the Middle East, North Africa, India...

  • Medical leech
  • Whipworm
    Whipworm
    The human tapworm is a roundworm, which causes trichuriasis when it infects a human large intestine. The name whipworm refers to the shape of the worm; they look like whips with wider "handles" at the posterior end.-Life cycle:The female T. trichiura produces 2,000–10,000 single celled eggs per day...

  • Immunotherapy
    Immunotherapy
    Immunotherapy is a medical term defined as the "treatment of disease by inducing, enhancing, or suppressing an immune response". Immunotherapies designed to elicit or amplify an immune response are classified as activation immunotherapies. While immunotherapies that reduce or suppress are...

  • Disease of affluence
  • Effects of parasitic worms on the immune system
    Effects of parasitic worms on the immune system
    The effects of parasitic worms, or helminths, on the immune system is a recently emerging topic of study among immunologists and other biologists. Experiments have involved a wide range of parasites, diseases, and hosts. The effects on humans have been of special interest...